Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

Glucagon is secreted from pancreatic a cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in b cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion

Whole-body vibration training induces hypertrophy of the human patellar tendon

I Brage finner du siste tekst-versjon av artikkelen, og den kan inneholde ubetydelige forskjeller fra forlagets pdf-versjon. Forlagets pdf-versjon finner du på onlinelibrary.wiley.com / In Brage you'll find the final text version of the article, and it may contain insignificant differences from the journal's pdf version. The definitive version is available at onlinelibrary.wiley.comAnimal studies suggest that regular exposure to whole-body vibration (WBV) induces an anabolic response in bone and tendon. However, the effects of this type of intervention on human tendon properties and its influence on the muscle-tendon unit function have never been investigated. The aim of this study was to investigate the effect of WBV training on the patellar tendon mechanical, material and morphological properties, the quadriceps muscle architecture and the knee extension torque–angle relationship. Fifty-five subjects were randomized into either a vibration, an active control, or an inactive control group. The active control subjects performed isometric squats on a vibration platform without vibration. Muscle and tendon properties were measured using ultrasonography and dynamometry. Vibration training induced an increase in proximal (6.3%) and mean (3.8%) tendon cross-sectional area, without any appreciable change in tendon stiffness and modulus or in muscle architectural parameters. Isometric torque at a knee angle of 90° increased in active controls (6.7%) only and the torque–angle relation remained globally unchanged in all groups. The present protocol did not appreciably alter knee extension torque production or the musculo-tendinous parameters underpinning this function. Nonetheless, this study shows for the first time that WBV elicits tendon hypertrophy in humans.Seksjon for fysisk prestasjonsevne / Department of Physical Performanc

Insulin-like growth factor 1 supplementation supports motor coordination and affects myelination in preterm pigs

IntroductionPreterm infants have increased risk of impaired neurodevelopment to which reduced systemic levels of insulin-like growth factor 1 (IGF-1) in the weeks after birth may play a role. Hence, we hypothesized that postnatal IGF-1 supplementation would improve brain development in preterm pigs, used as a model for preterm infants.MethodsPreterm pigs delivered by cesarean section received recombinant human IGF-1/IGF binding protein-3 complex (rhIGF-1/rhIGFBP-3, 2.25 mg/kg/day) or vehicle from birth to postnatal day 19. Motor function and cognition were assessed by monitoring of in-cage and open field activities, balance beam test, gait parameters, novel object recognition and operant conditioning tests. Collected brains were subject to magnetic resonance imaging (MRI), immunohistochemistry, gene expression analyses and protein synthesis measurements.ResultsThe IGF-1 treatment increased cerebellar protein synthesis rates (both in vivo and ex vivo). Performance in the balance beam test was improved by IGF-1 but not in other neurofunctional tests. The treatment decreased total and relative caudate nucleus weights, without any effects to total brain weight or grey/white matter volumes. Supplementation with IGF-1 reduced myelination in caudate nucleus, cerebellum, and white matter regions and decreased hilar synapse formation, without effects to oligodendrocyte maturation or neuron differentiation. Gene expression analyses indicated enhanced maturation of the GABAergic system in the caudate nucleus (decreased NKCC1:KCC2 ratio) with limited effects in cerebellum or hippocampus.ConclusionSupplemental IGF-1 during the first three weeks after preterm birth may support motor function by enhancing GABAergic maturation in the caudate nucleus, despite reduced myelination. Supplemental IGF-1 may support postnatal brain development in preterm infants, but more studies are required to identify optimal treatment regimens for subgroups of very or extremely preterm infants

Secretin release after Roux-en-Y gastric bypass reveals a population of glucose-sensitive S cells in distal small intestine

Abstract: Objectives: Gastrointestinal hormones contribute to the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB) on glycemic control. Secretin is secreted from duodenal S cells in response to low luminal pH, but it is unknown whether its secretion is altered after RYGB and if secretin contributes to the postoperative improvement in glycemic control. We hypothesized that secretin secretion increases after RYGB as a result of the diversion of nutrients to more distal parts of the small intestine, and thereby affects islet hormone release. Methods: A specific secretin radioimmunoassay was developed, evaluated biochemically, and used to quantify plasma concentrations of secretin in 13 obese individuals before, 1 week after, and 3 months after RYGB. Distribution of secretin and its receptor was assessed by RNA sequencing, mass-spectrometry and in situ hybridization in human and rat tissues. Isolated, perfused rat intestine and pancreas were used to explore the molecular mechanism underlying glucose-induced secretin secretion and to study direct effects of secretin on glucagon, insulin, and somatostatin secretion. Secretin was administered alone or in combination with GLP-1 to non-sedated rats to evaluate effects on glucose regulation. Results: Plasma postprandial secretin was more than doubled in humans after RYGB (P < 0.001). The distal small intestine harbored secretin expressing cells in both rats and humans. Glucose increased the secretion of secretin in a sodium-glucose cotransporter dependent manner when administered to the distal part but not into the proximal part of the rat small intestine. Secretin stimulated somatostatin secretion (fold change: 1.59, P < 0.05) from the perfused rat pancreas but affected neither insulin (P = 0.2) nor glucagon (P = 0.97) secretion. When administered to rats in vivo, insulin secretion was attenuated and glucagon secretion increased (P = 0.04), while blood glucose peak time was delayed (from 15 to 45 min) and gastric emptying time prolonged (P = 0.004). Conclusions: Glucose-sensing secretin cells located in the distal part of the small intestine may contribute to increased plasma concentrations observed after RYGB. The metabolic role of the distal S cells warrants further studies

Patellar tendon properties distinguish elite from non-elite soccer players and are related to peak horizontal but not vertical power

Purpose: The aims of our study were to investigate differences in tendon properties between elite and non-elite soccer players, and to establish whether tendon properties were related to power assessed during unilateral jumps in different directions. Methods: Elite (n=16; age, 18.1 ± 1.0yrs) and non-elite (n=13; age, 22.3 ± 2.7yrs) soccer players performed three repetitions of each type (unilateral vertical, unilateral horizontal-forward and unilateral medial) of countermovement jump (CMJ) on a force plate. Patellar tendon (PT) cross-sectional area (CSA), elongation, stiffness and Young’s modulus (measured at the highest common force interval) were assessed with ultrasonography and isokinetic dynamometry. Results: Elite soccer players demonstrated greater PT elongation (6.83±1.87 vs. 4.92±1.88 mm, P=0.011) and strain (11.73±3.25 vs. 8.38±3.06 %, P=0.009) than non-elite. Projectile range and peak horizontal power during unilateral horizontal-forward CMJ correlated positively with tendon elongation (r=0.657 and 0.693, P<0.001) but inversely with Young’s modulus (r=-0.376 and -0.402, P=0.044 and 0.031). Peak medial power during unilateral medial CMJ correlated positively with tendon elongation (r=0.658, P=<0.001) but inversely with tendon stiffness (r=-0.368, P=0.050). No tendon property correlated with unilateral vertical CMJ performance (r≤0.168; P≥0.204). Conclusions: Patellar tendon strain was greater in elite vs. non-elite soccer players and can therefore be considered an indicator of elite soccer playing status. Moreover, a more compliant patellar tendon appears to facilitate unilateral horizontal-forward and medial, but not vertical CMJ performance in soccer players. These findings should be considered when prescribing the detail of talent selection and development protocols related to direction-specific power in elite soccer players

Support for people who use Anabolic Androgenic Steroids: A Systematic Scoping Review into what they want and what they access.

BACKGROUND: Since there is a paucity of research on support for people using Anabolic Androgenic Steroids (AAS), we aimed to identify and synthesise the available evidence in this field. Gaining an understanding of the support both accessed and wanted by recreational AAS users will be of use to professionals who provide services to intravenous substance users and also to those working in the fields of public health and social care, with the aim to increase engagement of those using AAS. METHODS: A systematic scoping review of the literature to explore and identify the nature and scope of information and support both accessed and wanted by non-prescribed AAS users. Any support services or information designed to help people who use AAS were considered. RESULTS: We identified 23 papers and one report for review, which indicated that AAS users access a range of sources of information on: how to inject, substance effectiveness, dosages and side effects, suggesting this is the type of information users want. AAS users sought support from a range of sources including medical professionals, needle and syringe programmes, friends, dealers, and via the internet, suggesting that, different sources were used dependent on the information or support sought. DISCUSSION: AAS users tended to prefer peer advice and support over that of professionals, and access information online via specialist forums, reflecting the stigma that is experienced by AAS users. These tendencies can act as barriers to accessing services provided by professionals. CONCLUSIONS: Support needs to be specific and targeted towards AAS users. Sensitivity to their perceptions of their drug-use and the associated stigma of being classified in the same sub-set as other illicit drug users is relevant to facilitating successful engagement